Anti-inflammatory Naproxen Research Articles

Dual-Modality Accurate Visualization of Drug Synergy Based on Mass Spectrometry and Fluorescence Imaging.

There is a potential synergistic effect between nonsteroidal anti-inflammatory drugs and hydrogen sulfide (H2S), but direct evidence for the study is lacking. With a single fluorescence detection method, it is difficult to accurately confirm the effectiveness of the synergistic effect. In this study, the fluorescent probe and the nonsteroidal anti-inflammatory drug naproxen were combined via different self-immolative spacer groups to obtain a diagnostic and therapeutic integrated fluorescent probe Nap-NP-NSB, which can release H2S. The quantitative release of H2S by Nap-NP-NSB was evaluated in vitro and in cells, and the synergistic effect of H2S and naproxen was confirmed by monitoring the treatment process of cellular inflammation and oxidative damage of gastric mucosa cells. Finally, in vivo fluorescence imaging and mass spectrometry imaging of the liver and stomach tissues and their sections were performed in the mouse model of acute hepatitis. The dual-modal detection method not only confirmed that Nap-NP-NSB had better anti-inflammatory activity and less gastric mucosal damage, but also enabled a more accurate visualization of the drug synergistic effect of naproxen and H2S. This work provides a dual visualization imaging method combining fluorescence and mass spectrometry imaging and develops a new idea for studying drug synergies based on self-immolative structures.

Are Environmental Levels of Nonsteroidal Anti-Inflammatory Drugs a Reason for Concern? Chronic Life-Cycle Effects of Naproxen in Zebrafish.

The nonsteroidal anti-inflammatory drug naproxen (NPX) is among the most consumed pharmaceuticals worldwide, being detected in surface waters within the ng to μg/L range. Considering the limited chronic ecotoxicity data available for NPX in aquatic ecosystems, the present study aimed at evaluating its impact in the model organism Danio rerio, following a full life-cycle exposure to environmentally relevant concentrations (0.1 to 5.0 μg/L). An integration of apical endpoints, i.e., survival, growth, and reproduction, with gonad histopathology and gene transcription (RNA-seq) was performed to provide additional insights into the mode of action (MoA) of NPX. NPX decreased zebrafish growth and reproduction and led to histopathological alterations in gonads at concentrations as low as 0.1 μg/L. At the molecular level, 0.7 μg/L of NPX led to a disruption in gonads transcription of genes involved in several biological processes associated with reproduction, mainly involving steroid hormone biosynthesis and epigenetic/epitranscriptomic machineries. Collectively, these results show that environmentally realistic concentrations of NPX affect zebrafish reproduction and associated signaling pathways, indicating that current hazard and risk assessment data for NPX underestimate the environmental risk of this pharmaceutical.

Drug Binding to Partially Unfolded Serum Albumin: Insights into Nonsteroidal Anti-Inflammatory Drug Naproxen-BSA Interactions from Spectroscopic and MD Simulation Studies.

Understanding the binding details of a small-molecule drug to a protein in its partially unfolded state is important for drug delivery as it provides insight into the overall drug-binding ability of the protein, even when the majority of binding pockets in its unfolded state are impaired. The interaction of partially unfolded proteins with drugs remains poorly understood due to a lack of structural information on proteins in their partially unfolded states. Here, we studied the interaction between serum albumin (bovine serum albumin (BSA) as a model system), an abundant protein in blood serum that is an effective carrier for numerous known drugs, and a nonsteroidal anti-inflammatory drug (NSAID) naproxen (NPS) using various spectroscopic and computational methods. Molecular dynamics simulations starting from the drug-unbound state and performed at physiological and higher temperatures revealed novel hydrophobic sites on the BSA surface. We analyzed the BSA-NPS interaction in the presence and absence of the cationic organized assembly CTAB and two oligosaccharides (β-CD and 2-HP-β-CD) at different excitation wavelengths. The solvation dynamics of BSA under NPS-bound conditions became ∼4.6% faster. Oligosaccharides were found to increase the solubility of NPS by providing a hydrophobic environment for the formation of inclusion complexes through host-guest interactions. These findings provide a comprehensive overview and uncover the binding model and mechanism of interaction of NPS with BSA, revealing hydrophobic and electrostatic interactions and hydrogen bonds required for BSA to bind NPS at these noncanonical sites. The molecular-level understanding of the binding mechanism of commonly used NSAIDs like NPS with partially unfolded BSA will be useful in designing pharmaceutically important molecules with efficient loading and delivery properties.

Aqueous photolysis of naproxen exposed to UV and natural sunlight: Formation of excited triplet and photosensitizing product

Photochemical transformation is an important attenuation process for the non-steroidal anti-inflammatory drug naproxen (NPX) in both engineered and natural waters. Herein, we investigated the photolysis of NPX in aqueous solution exposed to both ultraviolet (UV, 254 nm) and natural sunlight irradiation. Results show that N2 purging significantly promoted NPX photolysis under UV irradiation, suggesting the formation of excited triplet state (3NPX*) as a critical transient. This inference was supported by benzophenone photosensitization and transient absorption spectra. Sunlight quantum yield of NPX was only one fourteenth of that under UV irradiation, suggesting the wavelength-dependence of NPX photochemistry. 3NPX* formed upon irradiation of NPX underwent photodecarboxylation leading to the formation of 2-(1-hydroxyethyl)-6-methoxynaphthalene (2HE6MN), 2-(1-hydroperoxyethyl)-6-methoxynaphthalene (2HPE6MN), and 2-acetyl-6-methoxynaphthalene (2A6MN). Notably, the conjugation and spin-orbit coupling effects of carbonyl make 2A6MN a potent triplet sensitizer, therefore promoting the photodegradation of the parent NPX. In hospital wastewater, the photolysis of NPX was influenced because the photoproduct 2A6MN and wastewater components could competitively absorb photons. Bioluminescence inhibition assay demonstrated that photoproducts of NPX exhibited higher toxicity than the parent compound. Results of this study provide new insights into the photochemical behaviors of NPX during UV treatment and in sunlit surface waters.

Novel Fe3O4 Nanoparticles with Bioactive Glass-Naproxen Coating: Synthesis, Characterization, and In Vitro Evaluation of Bioactivity.

Immune response to biomaterials, which is intimately related to their surface properties, can produce chronic inflammation and fibrosis, leading to implant failure. This study investigated the development of magnetic nanoparticles coated with silica and incorporating the anti-inflammatory drug naproxen, aimed at multifunctional biomedical applications. The synthesized nanoparticles were characterized using various techniques that confirmed the presence of magnetite and the formation of a silica-rich bioactive glass (BG) layer. In vitro studies demonstrated that the nanoparticles exhibited bioactive properties, forming an apatite surface layer when immersed in simulated body fluid, and biocompatibility with bone cells, with good viability and alkaline phosphatase activity. Naproxen, either free or encapsulated, reduced nitric oxide production, an inflammatory marker, while the BG coating alone did not show anti-inflammatory effects in this study. Overall, the magnetic nanoparticles coated with BG and naproxen showed promise for biomedical applications, especially anti-inflammatory activity in macrophages and in the bone field, due to their biocompatibility, bioactivity, and osteogenic potential.

Designing Powerful Biindole-Based Inherently Chiral Selectors: Enhancing Enantiodiscrimination by Core Functionalization with Additional Coordination Elements.

Among inherently chiral selectors of axial stereogenicity, usually resulting in very good enantiodiscrimination performances, the biindole-based family has the additional advantage of very easy functionalization of the two nitrogen atoms with a variety of substituents with desirable properties. Aiming to evaluate the possibility of exploiting such feature to enhance the enantiodiscrimination ability of the archetype structure, a series of three inherently chiral monomers were designed and synthesized, characterised by a 2,2'-biindole atropisomeric core conjugated to bithiophene wings enabling fast and regular electrooligomerization, and functionalised at the nitrogen atoms with an ethyl, a methoxyethyl, or a hydroxyethyl substituent. Nitrogen alkylation was also exploited to obtain for the first time the chemical resolution of the biindole selectors without employing chiral HPLC. The enantiodiscrimination ability of the selector series was comparatively evaluated in proof-of-concept chiral voltammetry experiments with a "benchmark" chiral ferrocenyl probe as well as with chiral non-steroidal anti-inflammatory drugs naproxen and ketoprofen. The large enantiomer potential differences for all probes increased in the ethyl < methoxyethyl ≪ hydroxyethyl sequence of selector substituents, supporting our assumption on the beneficial role of an additional coordination element. The powerful hydroxyethyl selector was also applied to ketoprofen in a commercial drug matrix.

A new multifunctional electrocatalyst based on PbS nanostructures decorated with graphene/polyaniline-modified glassy carbon electrode for selective detection of non-steroidal anti-inflammatory drug naproxen

Naproxen (NAP), a well-known anti-inflammatory drug, has also been considered for its antiviral prospective and acceptable potential for in vitro activity against serious respiratory syndrome-related coronavirus (SARS-CoV) and anti-influenza activity. However, designing a selective, sensitive and efficient electrocatalyst for the determination of NAP is still a great challenge. In this research, a new electrocatalytic sensor was constructed for the electrochemical recognition of NAP by a glassy carbon electrode modified with PbS nanostructures incorporated graphene/polyaniline nanocomposite. The synthesized samples were characterized by physicochemical analyses like EDS, XRD, FTIR, FESEM, and PL. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) were carried out to examine the electrocatalytic behavior of the modified electrodes. The EIS plot obviously demonstrated rapid electron transport at low frequencies for the PbS/graphene/PANI/GC electrode. It was observed that the PbS/graphene/PANI/GC electrode exhibited better-defined oxidation peaks, and greater peak currents for NAP detection compared to other electrodes. Under the optimum conditions, the proposed PbS/graphene/PANI nanoplatform provided a reliable linear range of 1 to 100 µM with a detection limit as low as 0.08 μM. Meanwhile, the PbS/graphene/PANI electrode possessed acceptable selectivity, good repeatability with an RSD of about 2.6 %, and a reduction of about 3 % after two weeks, and long-term stability of about 97 % of its original response for the recognition of NAP. Furthermore, the constructed electrode demonstrated NAP detection in real samples, such as human plasma and urine with good recoveries ranging from 98.8 % to 99.9 %, suggesting its promising prospects in clinical diagnostics.

Interaction of anti-inflammatory drug naproxen with essential amino acids: Quantitative thermodynamic insights

A combination of ultrasensitive isothermal titration calorimetry and uv–visible spectroscopy has been employed to unravel interaction of anti-inflammatory drug naproxen with five essential amino acids L-arginine, L-lysine, L-phenylalanine, L-valine and L-tryptophan. The nature of interaction in each case has been examined based on standard molar enthalpy of interaction ΔHmo and changes in the spectral properties. The values and sign of ΔHmo have been related with the nature of interacting groups and solvent reorganization as a result of drug-amino acid association. Exothermic standard molar enthalpy of interaction of naproxen with L-arginine indicated significant of polar interactions, and endothermic heat effects with all other amino acids suggested dominance of hydrophobic effect and desolvation penalty in the association process. The overall value of enthalpy of interaction for all the studied amino acids is less than 2 kJmol-1 suggesting that these interactions are not very strong. The uv–visible results provided support to ITC results in obtaining mechanistic insights into the nature of interactions. The results derive significance from the fact that sometimes anti-inflammatory drug naproxen may be administrated along with supplements of essential amino acids. In case there is a strong drug-amino acids interaction, efficacy of each one may be affected.

SrNiO3 perovskite synthesis for enhanced photodegradation of the nonsteroidal anti-inflammatory drug Naproxen: A clean and sustainable process for water treatment

The need to find effective and environmentally friendly ways to prevent pharmaceuticals from contaminating water is due to the growing concern about water pollution caused by hazardous organic pollutants. Photocatalysis is crucial for the degradation of organic pollutants. For this reason, many uses of nanostructured perovskite in various energy and environmental fields have aroused interest. The innovative aspect of this study is the use of SrNiO3 synthesis via the one-pot citrate nitrate method in photocatalysis. The sample was calcined at 450 °C and 900 °C for 5 h. Crystalline phase purity, morphology, surface area, pore size, and optical properties were investigated through X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET), Barrett-Joyner-Halenda (BJH), Fourier transform infrared spectroscopy (FTIR), and diffuse reflectance spectroscopy (DRS). The prepared sample of SrNiO3 was used as a photocatalyst for the photodegradation of naproxen, one of the most common pharmaceutical compounds detected in wastewater. The effects of catalyst dose, naproxen amount, and reaction kinetics were investigated. After 60 min of UV irradiation exposure, the photocatalytic removal efficiency was found to be optimal using 1 g/L of SrNiO3. In summary, perovskite SrNiO3 exhibited excellent physicochemical and mechanical stability after five cycles of reaction.

Chemical inhibition of Arabidopsis PIN-FORMED auxin transporters by the anti-inflammatory drug naproxen

The phytohormone auxin plays central roles in many growth and developmental processes in plants. Development of chemical tools targeting the auxin pathway is useful for both plant biology and agriculture. Here we reveal that naproxen, a synthetic compound with anti-inflammatory activity in humans, acts as an auxin transport inhibitor targeting PIN-FORMED (PIN) transporters in plants. Physiological experiments indicate that exogenous naproxen treatment affects pleiotropic auxin-regulated developmental processes. Additional cellular and biochemical evidence indicates that naproxen suppresses auxin transport, specifically PIN-mediated auxin efflux. Moreover, biochemical and structural analyses confirm that naproxen binds directly to PIN1 protein via the same binding cavity as the indole-3-acetic acid substrate. Thus, by combining cellular, biochemical, and structural approaches, this study clearly establishes that naproxen is a PIN inhibitor and elucidates the underlying mechanisms. Further use of this compound may advance our understanding of the molecular mechanisms of PIN-mediated auxin transport and expand our toolkit in auxin biology and agriculture.

PH-Sensitive Gold Nanorods for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Delivery and DNA-Binding Studies.

A facile experimental protocol for the synthesis of poly(ethylene glycol)-modified (PEGylated) gold nanorods (AuNRs@PEG) is presented as well as an effective drug loading procedure using the non-steroidal anti-inflammatory drug (NSAID) naproxen (NAP). The interaction of AuNRs@PEG and drug-loaded AuNRs (AuNRs@PEG@NAP) with calf-thymus DNA was studied at a diverse temperature revealing different interaction modes; AuNRs@PEG may interact via groove-binding and AuNRs@PEG@NAP may intercalate to DNA-bases. The cleavage activity of the gold nanoparticles for supercoiled circular pBR322 plasmid DNA was studied by gel electrophoresis while their affinity for human and bovine serum albumins was also evaluated. Drug-release studies revealed a pH-sensitive behavior with a release up to a maximum of 24% and 33% NAP within the first 180 min at pH = 4.2 and 6.8, respectively. The cytotoxicity of AuNRs@PEG and AuNRs@PEG@NAP was evaluated against MCF-7 and MDA-MB-231 breast cancer cell lines. The development of AuNRs as an efficient non-steroidal anti-inflammatory drugs (NSAIDs) delivery system for chemotherapy is still in its infancy. The present work can shed light and inspire other research groups to work in this direction.

Interactions between DMPC Model Membranes, the Drug Naproxen, and the Saponin β-Aescin.

In this study, the interplay among the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as a model membrane, the nonsteroidal anti-inflammatory drug naproxen, and the saponin β-aescin are investigated. The naproxen amount was fixed to 10 mol%, and the saponin amount varies from 0.0 to 1.0 mol%. Both substances are common ingredients in pharmaceutics; therefore, it is important to obtain deeper knowledge of their impact on lipid membranes. The size and properties of the DMPC model membrane upon naproxen and aescin addition were characterized with differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SAXS, WAXS), and photon correlation spectroscopy (PCS) in a temperature-dependent study. The interaction of all substances was dependent on the lipid phase state, which itself depends on the lipid's main phase transition temperature Tm. The incorporation of naproxen and aescin distorted the lipid membrane structure and lowers Tm. Below Tm, the DMPC-naproxen-aescin mixtures showed a vesicle structure, and the insertion of naproxen and aescin influenced neither the lipid chain-chain correlation distance nor the membrane thickness. Above Tm, the insertion of both molecules instead induced the formation of correlated bilayers and a decrease in the chain-chain correlation distance. The presented data clearly confirm the interaction of naproxen and aescin with DMPC model membranes. Moreover, the incorporation of both additives into the model membranes is evidenced.

Fluorescent sensing of non-steroidal anti-inflammatory drugs naproxen and ketoprofen by dansylated squaramide-based receptors.

Bis-squaramide receptors L1-L4 bearing a dansyl moiety were synthesised and their potential applications as fluorescent probes towards non steroidal anti-inflammatory drugs naproxen and ketoprofen was investigated. A detailed photophysical characterization in CH3CN/DMSO solution (9 : 1 v/v) was conducted and demonstrated that the two macrocyclic receptors L1 and L2 show good sensitivity towards ketoprofen with an ON-OFF fluorescent response, while the two open chain receptors L3 and L4 behave similarly with the three guests considered. DFT theoretical calculations carried out on L2 and L4 as model receptors allowed to propose a possible coordination mode towards the guests. Finally, 1H-NMR spectroscopy in DMSO-d6/0.5% water solution demonstrated that the four receptors interact with the considered guests via H-bonds.

Electrochemical oxidation of Naproxen in aqueous matrices: Elucidating the intermediates’ eco-toxicity, by assessing its degradation pathways via experimental and density functional theory (DFT) approaches

The removal of the non-steroidal anti-inflammatory drug (NSAID) Naproxen (NAX) in water by hydroxyl radicals (•OH) was performed by electrochemical advanced oxidation processes either with Pt or BDD anodes and a 3D carbon felt cathode. The degradation of NAX by (•OH vs electrolysis time) was well fitted to a pseudo-first-order reaction rate kinetic. The detected reaction intermediates (aromatic compounds and carboxylic acids) were experimentally monitored during the process via LC, while density functional theory (DFT) was applied to uncover undetected intermediates, some for the first time in literature. The formation of toxic intermediates with higher toxicity than NAX were identified, such as IMS4b (6-Methoxy-1-[1-(6-methoxynaphthalen-2-yl) ethyl] naphthalen-2-ol), catechol, and glycolic acid. Based on these data, a detailed oxidation pathway of NAX by •OH was proposed. The evolution of solution toxicity indicated that the formed toxic intermediates were subsequently removed during the TOC removal process. Finally, almost complete mineralization of NAX was achieved in simulated urine or wastewater by the electro-Fenton treatment, with an optimized dose of iron as catalyst, showing the EAOPs’ potential to efficiently remove NAX even from challenging matrices. In extension, the strategies developed can be applied to the treatment of other NSAIDs.

Pt(IV) Prodrugs with Non-Steroidal Anti-inflammatory Drugs in the Axial Position.

We report herein the design, synthesis, and biological investigation of a series of novel Pt(IV) prodrugs with non-steroidal anti-inflammatory drugs naproxen, diclofenac, and flurbiprofen, as well as these with stearic acid in the axial position. Six Pt(IV) prodrugs 5-10 were designed, which showed superior antiproliferative activity compared to cisplatin as well as an ability to overcome tumor cell line resistance to cisplatin. By tuning the drug lipophilicity via variation of the axial ligands, the most potent Pt(IV) prodrug 7 was obtained, with an enhanced cellular accumulation of up to 153-fold that of cisplatin and nanomolar cytotoxicity both in 2D and 3D cell cultures. Pt2+ species were detected at different depths of MCF-7 spheroids after incubation with Pt(IV) prodrugs using a Pt-coated carbon nanoelectrode. Cisplatin accumulation in vivo in the murine mammary EMT6 tumor tissue of BALB/c mice after Pt(IV) prodrug injection was proved electrochemically as well. The drug tolerance study on BALB/c mice showed good tolerance of 7 in doses up to 8 mg/kg.

Experimental and Theoretical Studies on the Intercalation of Naproxen into the Mg2Al and Zn2Al Layered Double Hydroxides by Ion Exchange Reaction

In this work, Layered Double Hydroxide (LDH) materials carrying the worldwide administered non-steroidal anti-inflammatory drug naproxen (NAP), and the sodium naproxenate salt (NaNAP) for comparison, were studied by computational approaches aiming to model the structure of hybrid LDH-drug and shed light on NAP intercalation process. Atomic modeling calculations were performed at the quantum mechanical level based on Density Functional Theory and classical force fields based on empirical interatomic potentials. LDHNAP materials were prepared by ion exchange reaction from Mg2Al(OH)6Cl and Zn2Al(OH)6Cl pristine phases. The characterization of the materials confirmed NAP intercalation and also the permanence of the pristine phases in the isolated materials after ion exchange. Crystallographic lattice parameters, elemental analysis, and TGA experimental results were then employed in the calculations, which revealed that NAP anions can completely neutralize the positive charge of the LDH layers: both Mg2Al and Zn2Al LDH structures could be optimized with all Cl− anions substituted by NAP. The drug assumed different dispositions in the NaNAP crystal or when intercalated into LDH. Additionally, infrared wavenumbers calculations agreed with the experimental results and showed useful to support LDHNAP bands assignment. The employed theoretical models to represent the structure of LDHNAP systems are expected to assist the interpretation of future experimental results and to be used as auxiliary tools to tune properties of LDH-drug pharmaceutical formulations.

Development and evaluation of Pirkle-type chiral stationary phase for flash chromatography

Liquid chromatography is the most applied methodology for enantioseparation in preparative and semi-preparative scale; however, flash chromatography is seldom the first choice. This work proposes a new sustainable method to achieve pure enantiomers in mg scale. Herein, the functionalization of silica for flash chromatography columns with a suitable chiral selector, for subsequent quantitative enantioseparation of chiral compounds, is described. Accordingly, the Whelk-O®1 chiral selector was bonded to flash silica and packed into a reused solid phase extraction cartridge. For the evaluation of the enantioselective performance of the flash column, the enantiomers of a chiral derivative of xanthone were quantitatively enantioseparated with an average recovery of 70% and an enantiomer ratio (e.r.) of 99% and 97% for each enantiomer. Evaluation with the anti-inflammatory drug naproxen was also performed, resulting in an average recovery of 95% and 89% and 95% e.r. for each enantiomer. The flash column showed high stability and load ability, versatility, and good reproducibility.

Evaluation of in vitro and in silico anti-inflammatory potential of some selected medicinal plants of Bangladesh against cyclooxygenase-II enzyme

Ethnopharmacological relevanceMedicinal plants are sources of chemical treasures that can be used in treatment of different diseases, including inflammatory disorders. Traditionally, Heritiera littoralis, Ceriops decandra, Ligustrum sinense, and Polyscias scutellaria are used to treat pain, hepatitis, breast inflammation. The present research was designed to explore phytochemicals from the ethanol extracts of H. littoralis, C. decandra, L. sinense, and P. scutellaria to discern the possible pharmacophore (s) in the treatment of inflammatory disorders. Material and methodsThe chemical compounds of experimental plants were identified through GC-MS analysis. Furthermore, in-vitro anti-inflammatory activity was assessed in human erythrocytes and an in-silico study was appraised against COX-2. ResultsThe experimental extracts totally revealed 77 compounds in GC-MS analysis and all the extracts showed anti-inflammatory activity in in-vitro assays. The most favorable phytochemicals as anti-inflammatory agents were selected via ADMET profiling and molecular docking with specific protein of the COX-2 enzyme. Molecular dynamics simulation (MDS) confirmed the stability of the selected natural compound at the binding site of the protein. Three phytochemicals exhibited the better competitive result than the conventional anti-inflammatory drug naproxen in molecular docking and MDS studies. ConclusionBoth experimental and computational studies have scientifically revealed the folklore uses of the experimental medicinal plants in inflammatory disorders. Overall, N-(2-hydroxycyclohexyl)-4-methylbenzenesulfonamide (PubChem CID: 575170); Benzeneethanamine, 2-fluoro-. beta., 3, 4-trihydroxy-N-isopropyl (PubChem CID: 547892); and 3,5-di-tert-butylphenol (PubChem CID: 70825) could be the potential leads for COX-2 inhibitor for further evaluation of drug-likeliness.

Trinuclear silver(I) complex of non-steroidal anti-inflammatory drug naproxen: Synthesis, characterization, and in vitro cytotoxicity

Herein, a new silver(I) complex with the non-steroidal anti-inflammatory drug naproxen and nitrogen donor 3-picoline ligands was synthesized, characterized, and subsequently tested for its cytotoxicity against different types of cancer cell lines. Elemental analysis, Fourier transform infrared spectroscopy, thermal, and proton nuclear magnetic resonance techniques showed that the molecular formula of the prepared complex is bis(3-picoline)tris(m-naproxenato)trisilver(I) and naproxen ligands bind to silver ions in a bridging bidentate mode. 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) results revealed that silver salts and naproxen alone showed quite weak cytotoxic activity against human breast adenocarcinoma (MDA-MB-453), lung adenocarcinoma (A-549), and colorectal adenocarcinoma (HT-29) cell lines (IC50 &gt; 250 µM), whereas the complex displayed dose dependent cytotoxicity against the aforementioned cell lines. The highest cytotoxicity was observed on MDA-MB-453 cells with an IC50 value of 11.73 µM. Moreover, the complex showed higher selectivity against the cancer cell lines compared to fibroblast 3T3-L1 cells. This study provides preliminary scientific data on the complex for further elucidation of its anticancer mechanism of action.

HSA nanoparticles in drug recognition: mechanistic insights with naproxen, diclofenac and methimazole

Protein-based nanoparticles offer a suitable targeted delivery platform to drugs in terms of biocompatibility, biodegradability and abundance in nature. Physicochemical understanding of drug encapsulation by protein nanoparticles and their impact on protein aggregation is essential. In this work, we have examined quantitative aspects of encapsulation of non-steroidal anti-inflammatory drugs naproxen and diclofenac sodium, and anti-thyroid drug methimazole in nanoparticles of human serum albumin (HSA NPs) by using ultrasensitive calorimetry. Thermodynamic signatures accompanying the interactions revealed that the partitioning of all these drugs in HSA NPs is primarily driven via contributions from desolvation of highly hydrated nanoparticles surface. Furthermore, the effect of these nanoparticles on fibrillation of HSA has also been studied. HSA NPs are determined to be ineffective towards inhibition of fibrillation under employed conditions. However, the extent of inhibition by HSA NPs varies depending upon the structural characteristics of the drugs. Such studies help to gain mechanistic aspects on drug loading into protein-based nanoparticles and are expected to provide useful insights into improving existing nano-drug carriers and their efficiency in preventing protein fibrillation. Communicated by Ramaswamy H. Sarma